Theileriosis is the most significant disease of livestock in many areas of Africa and is a major obstacle to the development of all forms of the cattle industry on the African continent. East Coast Fever (ECF) is a debilitating and often lethal form of theileriosis caused by the parasite, Theileria parva parva which affects the cattle population in East and Central Africa. ECF has been reported as the cause of half a million cattle deaths per year in East Africa alone. Cattle are infected by ticks carrying t he disease. In an ECF infection, lymphoid cells are first infected and transformed resulting in large infected lymphoblastoid cells which divide regularly to produce two infected daughter cells. This lymphoproliferative phase is followed by a lympodestructive phase when merozoites are liberated from the infected lymphoid cells accompanied by lymphotoxic effects. While the economic losses resulting from ECF mortality are tremendous, additional significant losses may result from reduced productivity, the expense of treatment and control, and the exclusion of more productive breeds of cattle from endemic regions.
Treatment and control measures of both the organism and the tick vector of theileriosis have been difficult due to obstacles presented by the pathogenesis of the disease, contacts between domestic herds, contacts between wild and domestic animals, extensive range areas, cultural and logistic management practices, cost, and geopolitical constraints. While progress has been made in the areas of chemotherapy and immunization, significant problems continue to exist in the control of ECF by these methods.
Parasite infections also afflict man, one of the most common of such infections being malaria, a disease whose treatment still today presents a significant challenge to the medical community.
Several mechanisms of the immune system contribute to anti-parasite host defense. A recent review reported that gamma interferon may be efficacious in the treatment of protozoal infections while alpha or beta interferon has shown little activity. Currently accepted therapeutic treatment regimens for interferon responsive diseases dictate the use of high concentrations of interferon administered intradermally, intravenously, or intramuscularly. However, recent studies using low doses of human alpha interferon and human beta interferon administered orally have shown significant benefits in the stimulation of immunologic variables and in the treatment of diseases of cattle, swine, horses, chickens, cats, dogs and humans.
In accordance with this invention, it has been found that oral treatment with low doses of interferon in a form that Promotes its contact with the oral and pharyngeal mucosa prevents the development of parasitic infections in human and animal hosts exposed to infectious parasites. Effective doses range from about 0.1 to about 10 IU of interferon per kg of host weight. Dosage forms can be solid or semi-solid (gel or paste) or liquid, the solid dosage forms being adapted for dissolving in the host's/patient's mouth.
"Interferon" is a term generically comprehending a group of vertebrate glycoproteins and proteins which are known to have various biological activities, such as antiviral, antiproliferative and immunomodulatory activity, at least in the species of the animal in which such substances are derived. The following definition of "interferon" has been accepted by an international committee assembled to devise a system for the orderly nomenclature of interferons: "To qualify as an interferon a factor must be a protein which exerts virus non-specific, antiviral activity at least in homologous cells through cellular metabolic process involving synthesis of both RNA and protein." Journal of Interferon Research, 1, pp. vi (1980). "Interferon" as used herein in describing the present invention shall be deemed to have that definition and shall contemplate proteins, including glycoproteins, regardless of their source or method of preparation or isolation.
Interferons have generally been named in terms of the species of animal cells producing the substance (e.g., human, murine, bovine, etc.), the type of cell involved (e.g., leukocyte, lymphoblastoid, fibroblast) and, occasionally, the type of inducing material responsible for the interferon production (e.g., virus, immune). Interferon has been loosely classified by some researchers according to the induction mode as either Type I or Type II, with the former classification comprehending viral and nucleic acid induced interferon, and the latter class including the material produced as a lymphokine through induction by antigens and mitogens. More recently, an orderly nomenclature system for interferon has been devised which classifies interferons into types on the basis of antigenic specificities. Under this newer classification system, the designations alpha, beta and gamma have been used to correspond to previous designations of leukocyte, fibroblast and Type II (immune) interferons, respectively. Alpha and beta interferons are usually acid-stable and correspond to what have been called Type I interferons. Gamma interferons are usually acid-labile and correspond to what have been called Type II interferons.
The use of interferon for the treatment of disease in man and animals has been the subject of intense on-going research efforts in many laboratories, both in industry and in educational institutions around the world. In some of the earliest research activities interferon was shown to have antiviral properties and the most successful clinical therapeutical applications to date have been in the treatment of virus-related disease states. More recently it has been found that exogenous interferon is effective for the regression or remission of some metastatic disease states. The literature is replete with reports of research and development efforts directed to defining activities and potential therapeutic uses of interferon. Most of the reports described activities of interferon in vitro or its effects in vivo following parenteral, particularly intramuscular and intradermal administration. There have been some reports of successful topical and intranasal usages. It has seldom been administered intravenously because of substantial adverse effects attributable to "contaminants" in crude and even highly purified isolates. While the advent of recombinant DNA technology has allowed production of pure interferon species, intravenous administration of such pure compositions are not without adverse effects. The Food and Drug Administration has approved the use of alpha-interferon administered parenterally in high doses for the treatment of human hairy cell leukemia and for several other indications.
Before the first report of a successful oral administration of interferon in now issued U.S. Pat. No. 4,462,985, there was no recognition in the art of the potential offered by oral administration of interferon. The generally held belief was that interferon could not survive the digestive conditions of the alimentary canal. Since the first disclosure of the immunotherapeutic benefit achieved via oral administration of interferon, we have continued to investigate the efficacy of orally administered interferon. U.S. Pat. No. 4,497,795, issued Feb. 5 1985, describes and claims the use of interferon administered orally or via intravenous administration to stimulate appetite and feed efficiency of animal species. U.S. patents have also issued for the use of interferon at dosages less than about 5 IU/lb of body weight for increasing feed efficiency and food utilization in warm-blooded vertebrates, for preventing and treating shipping fever, and for enhancing vaccine efficiency. More recently, it was discovered that the efficacy of orally administered interferon can be realized simply by administering it in a form which promotes contact of the interferon dosage with the mucosal lining of the mouth and throat.